The present invention relates generally to drug and gene delivery and pertains more particularly to an electrode assembly for an apparatus for a method of trans-surface delivery of genes, drugs, and other molecules through tissue surfaces.
The medical community has long sought improved methods of trans-surface delivery of drugs, genes such as DNA, portions of DNA, chemical agents, or other molecules without physical penetration or invasion of the tissue surface. Several methods involve the electroporation of the tissue surface through the application of an electrical field by means of electrodes on the tissue surface. The field is applied at a predetermined strength and duration in order to make the walls of the tissue surface transiently permeable to permit the molecules to pass through the tissue surface into the underlying tissue. Further electroporation can enable the molecules to enter preselected cells without damaging them. The voltage that must be applied is proportional to the distance between the electrodes. When the space between the electrodes is too great, the generated electric field penetrates deep into the tissue where it causes unpleasant nerve and muscle reaction. The molecules are placed in close proximity to the cells, either in the interstitial tissue surrounding the cells or in a fluid medium containing the cells.
Electroporation can be carried out by a sophisticated electroporation system having programmable power sequence and duration programmed in. For example, a suitable system is disclosed in co-pending application Ser. No. 08/709,615 filed Sep. 9, 1996, entitled ELECTROPORATION EMPLOYING USER-CONFIGURED PULSING SCHEME, now U.S. Pat. No. 5,869,326, granted which is incorporated herein by reference as though fully set forth.
Broadly, the above referenced invention concerns an electroporation apparatus for and method of generating and applying an electric field according to a user-specified pulsing scheme. One example of such a pulsing scheme includes a low voltage pulse of a first duration, immediately followed by a high voltage pulse of a second duration, and immediately followed by a low voltage pulse of a third duration. The low voltage field acts to accumulate molecules at the tissue surface, the appropriately high voltage field acts to create an opening in the tissue surface, and the final low voltage field acts to move the molecules through the tissue surface.
While electroporation provides new pathways through the tissue surface for passages of molecules, it does not provide a needed driving force to those molecules to move them through the tissue surface. As a result, it is desirable to combine electroporation with techniques for providing a driving force such as pressure, ultrasound, electroincorporation, and iontophoresis. First, pressure can be applied mechanically by pressing on the electrode assembly with any suitable means for applying a reasonably uniform pressure over the desired area. Second, ultrasound can be applied by an ultrasound source. Third, electroincorporation can be applied to transport molecules through the tissue surface into the tissue. Fourth, iontophoresis can be applied as the driving force.
Iontophoresis alone, wherein low voltage is applied between widely spaced electrodes for a long period of time, can transport charged molecules through existing pathways such as hair follicles and sweat glands. However, the volumes of molecules transported for a unit of time is very small, and insufficient for many applications. Combining electroporation and iontophoresis can increase the amount transported initially while the created pathways are open. The paths created by the electroporation stay open for a short period of time and then close.
One example of a surface for the trans-surface delivery of molecules is the skin or the stratum corneum (SC). The SC consists of a thin layer of dead cells with a high electrical resistance which presents a major obstacle to the administration of drugs and genes transdermally. However, this layer can be perforated by the administration of short high voltage pulses, which create a dielectric breakdown of the SC forming pores which can allow the passage of molecules.
The tissue surfaces to which the medical profession would like to apply electroporation vary by their size, shape, location, porosity, and accessability, among others. It is desirable that an electrode assembly for an apparatus for and a method of trans-surface molecular delivery be available to accommodate a wide variety of these tissue surfaces.